This application constitutes the first renewal of the Mt. Sinai School of Medicine Alzheimer's Disease Research Center. The cores will manage and coordinate the various components of the Center (Administrative Core); obtain, characterize, and distribute to investigators postmortem tissues from AD victims and appropriate controls (Neuropathology Core); recruit and assess all new patients with AD and controls necessary for clinical studies and perform data management and analysis (Clinical Research Support Core); and educate and inform the public sector and caregivers who are affected by AD (Information Transfer Core). The ADRC will engage in a series of diverse studies using molecular and cellular approaches as well as traditional methods of biological psychiatry and clinical neuroscience. Studies on the possible role of differential processing of the amyloid precursor protein in the development of the plaques of in AD will be undertaken by Dr. Robakis and his colleagues. Dr.Lazzarini will use transgenic procedures to investigate the mechanisms controlling the expression of neurofilament proteins in diseased and normal brain. Detailed investigation of the cortex cortical tracts that undergo degeneration in AD will be conducted by Dr. John Morrison, whose colleague Dr. Dan Perl will continue his pioneer studies on the role of aluminum in the histopathology of AD. Dr. Haroutunian will continue his work on animal models of Alzheimer's Disease exploring, the effects of a serotonin deficiency upon animals both with and without a nucleus basalis lesion. We will extend his work on noradrenergic and cholinergic deficient animals to determine what noradrenergic agents are best able to reverse the behavioral consequences of a partial noradrenergic lesion. Dr. Kenneth Davis will determine if a simple marker of noradrenergic neurotransmission is an antemortem predictor of treatment response to cholinesterase inhibitors or cholinesterase inhibitors combined with noradrenergic agents. Finally Dr. Richard Mohs will extend ongoing studies on the relationship between the hypothalamic pituitary adrenal axis and_the progression of AD.